A large segment of the female population is affected by premenstrual syndrome (PMS) and menopausal symptoms. Limited medical treatments are available, some with severe adverse effects. Instead, many women have turned to botanical dietary supplements. Angelica sinensis (Oliv.) Diels is one of the most commonly used botanical dietary supplements for the relief of PMS and menopausal symptoms. Although the dried root of thi plant, also known as Dong quai, has been used traditionally in China for centuries and is currently being used by many American women, its mechanisms of action are poorly understood. We hypothesize that Angelica sinensis can act through CNS receptors to exhibit beneficial effects in PMS and menopause. In the original application, we propose to test this hypothesis by first evaluating the affinity of several chemically characterized Angelica sinensis extracts to the opiate and 3-aminobutyric acid (GABA)-A receptors. The extracts will be further tested for their activation of opiate receptors by measuring G protein activation and adenylyl cyclase inhibition and the activation of the GABA(A) receptor by determining GABA-gated Cl- influx in synaptosomes. Aim 3 will determine the in vivo efficacy of two extracts in a rat model. In the revised application, we propose to expand the scope of research to include other relevant CNS receptor and transporter systems. Accordingly, the new aim 4 will examine the affinity of these extracts to the monoamine receptors and transporters. The additional studies will accelerate the tempo of scientific research and allow for job creation. Results from these studies will help to define the molecular mechanisms of action of Angelica sinensis. Such information will not only provide mechanistic evidence for the use of Angelica sinensis in relieving PMS and menopausal symptoms, but may also be used to biologically standardize an Angelica sinensis product for future clinical studies. PUBLIC HEALTH RELEVANCE: A large segment of the female population is affected by premenstrual syndrome (PMS) and menopausal symptoms. Although Angelica sinensis (Oliv.) Diels is one of the most commonly used botanical dietary supplements for the relief of PMS and menopausal symptoms, little is known for its mechanisms. This application aims to apply molecular methods to study mechanisms of action of Angelica sinensis. The competitive revision will expand the scope of research to address the possible mechanisms of action through the monoamine receptors and transporters for Angelica sinensis. In addition to the new knowledge to be gained, the revised aims will accelerate the tempo of scientific research and allow for job creation through direct hiring of additional staff and indirect impact due to increased research activity and expenditure.